Recent studies have shown that Connexin43 mimetic peptide (Cx43 MP) can prevent secondary damage following retinal ischaemic and inflammatory disorders by blocking uncontrolled Cx43 hemichannel opening. However, limitations in peptide stability and the presence of various intraocular barriers limit efficient retinal delivery in the clinical setting. The present study aimed to achieve targeted and sustained peptide delivery to the retina by encapsulating Cx43 MP into hyaluronic acid (HA) coated albumin nanoparticles (NPs). Intraocular biodistribution, particle retention, retinal targeting, and therapeutic efficacy of intravitreally injected NPs encapsulating Cx43 MP were evaluated in a rat model of retinal ischaemia-reperfusion injury. NPs rapidly diffused through the vitreous and specifically targeted CD44-expressing retinal cells. NPs remained at the target side for extended periods enabling sustained peptide release and thus prolonged therapeutic action. Compared to free Cx43 MP, Cx43 MP loaded NPs enabled enhanced therapeutic efficacy preventing thinning of retinal layers and disruption of retinal blood vessels. Immunohistochemical results confirm that Cx43 MP loaded NPs efficiently reduced Cx43 expression, thereby suppressing ongoing inflammation and preventing the loss of retinal ganglion cells. Overall, HA coated NPs could have great potential as a peptide delivery platform in the treatment of chronic retinal degenerative and inflammatory disorders.

最近的研究表明，Connexin43模拟肽（Cx43 MP）可以通过阻止不受控制的Cx43半通道开放来预防视网膜缺血和炎症性疾病继发性损伤。然而，在临床环境中，肽稳定性的限制和各种眼内屏障的存在限制了有效的视网膜递送。本研究旨在通过将Cx43 MP封装到透明质酸（HA）包被的白蛋白纳米颗粒（NPs）中，实现向视网膜的靶向和持续肽递送。在视网膜缺血再灌注损伤的大鼠模型中评估了玻璃体内注射包裹Cx43 MP的NP的眼内生物分布，颗粒保留，视网膜靶向和治疗效果。NPs快速扩散通过玻璃体和专门针对CD44表达的视网膜细胞。NPs在靶标侧停留的时间更长，可以持续释放肽，从而延长治疗作用。与游离Cx43 MP相比，负载Cx43 MP的NP能够增强治疗功效，防止视网膜层变薄和视网膜血管破裂。免疫组织化学结果证实，载有Cx43 MP的NP可有效降低Cx43的表达，从而抑制正在进行的炎症并防止视网膜神经节细胞的丢失。总体而言，用HA包被的NPs作为治疗慢性视网膜变性和炎症性疾病的肽传递平台具有巨大潜力。装载Cx43 MP的NP能够增强治疗功效，防止视网膜层变薄和视网膜血管破裂。免疫组织化学结果证实，载有Cx43 MP的NP可有效降低Cx43的表达，从而抑制正在进行的炎症并防止视网膜神经节细胞的丢失。总体而言，用HA包被的NPs作为治疗慢性视网膜变性和炎症性疾病的肽传递平台具有巨大潜力。装载Cx43 MP的NP能够增强治疗功效，防止视网膜层变薄和视网膜血管破裂。免疫组织化学结果证实，载有Cx43 MP的NP可有效降低Cx43的表达，从而抑制正在进行的炎症并防止视网膜神经节细胞的丢失。总体而言，用HA包被的NPs作为治疗慢性视网膜变性和炎症性疾病的肽传递平台具有巨大潜力。